Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, lymphomas and leukemias. Transitions predominate in cancers of the colon, brain and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. The distributions of mutations in the p53 sequence are also distinct. Most transitions in colorectal carcinomas, brain tumors, leukemias and lymphomas are at CpG dinucleotide mutational hotspots (codons 175, 248, 273 and 282). G to T transversions in lung, breast and esophageal carcinomas are dispersed among numerous codons, whereas in liver tumors from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors in human carcinogenesis. A receptor protein tyrosine phosphatase, PTP gamma, is a candidate tumor suppressor gene on human chromosome 3p2l that may be involved in human lung and renal carcinogenesis. An antimetastasis gene, nm23, is frequently altered in human lung, breast and renal cancers.